Two major objectives will e pursued: 1. a study on the composition of tears in a prototype neuroimmune disorder (multiple sclerosis [MS]) which may involve abnormalities in mucosal immunity; and 2. how the nervous system may alter tear flow and composition in patients with neurolacrimal deficits. 1. Preliminary data suggests the MS tear immunoglobulins (Ig) differ from normal tears. This may impair the ability of MS patients to protect the host against neurotropic viruses that have been implicated in MS. MS tears and saliva will be examined for abnormalities in Ig, viral specific antibodies (Ab), the relative amounts of dimeric and monomeric IgA (using ELISA); and immunological markers (oligoclonal bands, Ab to myelin basic protein, distinct protein bands) using SDS polyacrylamide gel electrophoresis, immunoblot, and 2-dimensional electrophoresis. Mucosal integrity will be studies by looking for circulating Antigen-Ab complexes to normally excluded dietary proteins. The presence of viral specific immune complexes will be correlated with viral Ab in secretory fluids. A defect in secretory IgA in MS will be investigated by comparing T alpha levels and in vitro polymeric IgA production of MS peripheral cells vs control cells using rosette assay and ELISA. 2. The autonomic nervous system (ANS) may modulate the secretion of Ig. The role of the nervous system in Ig secretion will be examined by comparing interocular differences in patients with unilateral neurolacrimal deficits (facial neuropathy, corneal hypestheisa and Horners syndrome); and by examining tear Ig before and after various forms of reflex stimulation in normals. Tear kinetics of the lacrimal reflexes will also be studied. The possibility that dysautonomia may be an important factor in the genesis of idiopathic cases of dry eye will be explored first by studying tear kinetics of lacrimal gland denervation and supersensitivity to cholinergic agonists in patients with neurolacrimal hyposecretion due to facial neuropathies. Similar studies will be performed on patients with idiopathic dry eye and Sjogren's syndrome. These studies should result in normative immunological data on tears and will define neural factors in lacrimation and mucosal immunity. Ultimately, the effective treatment of dry eye will be based on a clear understanding of how the ANS regulates tear flow.